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Tail Anchored protein insertion mediated by CAML and TRC40 links to neuromuscular function in mice.

PLoS Genet

January 2025

Department of Pediatric and Adolescent Medicine, Mayo Clinic, 200 1st St. SW, Rochester, Minnesota 55905, United States of America.

Motor neuron diseases, such as amyotrophic lateral sclerosis (ALS) and progressive bulbar palsy, involve loss of muscle control resulting from death of motor neurons. Although the exact pathogenesis of these syndromes remains elusive, many are caused by genetically inherited mutations. Thus, it is valuable to identify additional genes that can impact motor neuron survival and function.

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Activation of locus coeruleus noradrenergic neurons rapidly drives homeostatic sleep pressure.

Sci Adv

January 2025

Department of Neuroscience, Helen Wills Neuroscience Institute, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA.

Homeostatic sleep regulation is essential for optimizing the amount and timing of sleep for its revitalizing function, but the mechanism underlying sleep homeostasis remains poorly understood. Here, we show that optogenetic activation of locus coeruleus (LC) noradrenergic neurons immediately increased sleep propensity following a transient wakefulness, contrasting with many other arousal-promoting neurons whose activation induces sustained wakefulness. Fiber photometry showed that repeated optogenetic or sensory stimulation caused a rapid reduction of calcium activity in LC neurons and steep declines in noradrenaline/norepinephrine (NE) release in both the LC and medial prefrontal cortex (mPFC).

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Viruses engage in a variety of processes to subvert host defenses and create an environment amenable to replication. Here, using rotavirus as a prototype, we show that calcium conductance out of the endoplasmic reticulum by the virus encoded ion channel, , induces intercellular calcium waves that extend beyond the infected cell and contribute to pathogenesis. Viruses that lack the ability to induce this signaling show diminished viral shedding and attenuated disease in a mouse model of rotavirus diarrhea.

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Action potential-independent spontaneous microdomain Ca transients-mediated continuous neurotransmission regulates hyperalgesia.

Proc Natl Acad Sci U S A

January 2025

Department of Neurology, the Second Affiliated Hospital, Neuroscience Research Center, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710000, China.

Neurotransmitters and neuromodulators can be released via either action potential (AP)-evoked transient or AP-independent continuous neurotransmission. The elevated AP-evoked neurotransmission in the primary sensory neurons plays crucial roles in hyperalgesia. However, whether and how the AP-independent continuous neurotransmission contributes to hyperalgesia remains largely unknown.

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Postoperative delirium (POD), an acute cognitive dysfunction linked to morbidity and mortality, is characterized by memory impairments and disturbances in consciousness, particularly in patients aged 65 and older. Neuroinflammation and NAD+ imbalance are key mechanisms behind POD, leading to synaptic and cognitive deterioration. However, how surgery contributes to POD and neuroinflammation remains unclear, and effective treatments are lacking.

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